GRHL1

grainyhead like transcription factor 1

Basic information

Region (hg38): 2:9951693-10002277

Previous symbols: [ "TFCP2L2" ]

Links

ENSG00000134317 ∙ NCBI:29841 ∙ OMIM:609786 ∙ HGNC:17923 ∙ Uniprot:Q9NZI5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRHL1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRHL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			32			32
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	33	0	1

Variants in GRHL1

This is a list of pathogenic ClinVar variants found in the GRHL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-9954974-C-G		not specified	Uncertain significance (Jul 20, 2021)
2-9955015-C-T		not specified	Uncertain significance (Jul 19, 2023)
2-9955045-A-C		not specified	Uncertain significance (Jun 26, 2024)
2-9955068-C-G			Benign (May 21, 2018)
2-9958839-G-C		not specified	Uncertain significance (Aug 16, 2021)
2-9958841-C-G		not specified	Uncertain significance (Mar 18, 2024)
2-9958846-C-A		not specified	Uncertain significance (Feb 01, 2023)
2-9961068-G-A		not specified	Uncertain significance (Nov 21, 2022)
2-9961071-C-A		not specified	Uncertain significance (Jan 23, 2024)
2-9961117-A-C		not specified	Uncertain significance (May 09, 2023)
2-9961159-G-A		not specified	Uncertain significance (Jun 29, 2023)
2-9961266-G-T		not specified	Uncertain significance (Aug 10, 2024)
2-9961267-C-T		not specified	Uncertain significance (Dec 20, 2023)
2-9961305-A-G		not specified	Uncertain significance (Sep 08, 2024)
2-9961338-A-G		not specified	Uncertain significance (Jun 29, 2023)
2-9961359-G-C		not specified	Uncertain significance (May 31, 2023)
2-9961362-G-A		not specified	Uncertain significance (Jul 15, 2024)
2-9962482-C-T		not specified	Uncertain significance (Sep 09, 2021)
2-9963948-C-T		not specified	Uncertain significance (Sep 26, 2023)
2-9964030-C-G		not specified	Uncertain significance (Nov 10, 2024)
2-9964322-G-A		not specified	Uncertain significance (Oct 03, 2022)
2-9965313-A-G		not specified	Uncertain significance (Jul 30, 2024)
2-9986209-C-T		not specified	Uncertain significance (Dec 20, 2023)
2-9986248-G-A		not specified	Uncertain significance (Jan 19, 2024)
2-9990724-A-C		not specified	Uncertain significance (Dec 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRHL1	protein_coding	protein_coding	ENST00000324907	16	57071

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.239	0.760	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.68	258	346	0.745	0.0000190	4078
Missense in Polyphen		97	146.02	0.66431		1726
Synonymous	0.539	127	135	0.941	0.00000809	1153
Loss of Function	4.11	8	33.7	0.237	0.00000188	394

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000193	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000533	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor involved in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' (PubMed:12175488, PubMed:18288204, PubMed:29309642). Important regulator of DSG1 in the context of hair anchorage and epidermal differentiation, participates in the maintenance of the skin barrier. There is no genetic interaction with GRHL3, no functional cooperativity due to diverse target gene selectivity during epithelia development (By similarity). {ECO:0000250|UniProtKB:Q921D9, ECO:0000269|PubMed:12175488, ECO:0000269|PubMed:18288204, ECO:0000269|PubMed:29309642}.; FUNCTION: Isoform 2: May function as a repressor in tissues where both isoform 1 and isoform 2 are expressed. {ECO:0000269|PubMed:12175488}.
• Pathway: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) (Consensus)

Recessive Scores

• pRec: 0.201

Intolerance Scores

• loftool: 0.453
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.26

Haploinsufficiency Scores

• pHI: 0.181
• hipred: Y
• hipred_score: 0.654
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.901

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Grhl1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: grhl1
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: desmosome organization;regulation of transcription by RNA polymerase II;epidermis development;regulation of lipid metabolic process;regulation of keratinocyte differentiation;positive regulation of transcription by RNA polymerase II;establishment of skin barrier
• Cellular component: nucleus;nucleoplasm;Golgi apparatus;cytosol;intracellular membrane-bounded organelle
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;chromatin DNA binding;protein homodimerization activity;sequence-specific DNA binding;transcription regulatory region DNA binding